P969: VRD OUTPERFORMED VCD AS INDUCTION THERAPY BEFORE FIRST-LINE ASCT IN MULITPLE MYELOMA; RESULTS FROM A NATIONWIDE, POPULATION-BASED STUDY
Authors: Jakob Nordberg Nørgaard, Kari Lenita Falck Moore, Tobias Slørdahl, Anders Vik, Tor Henrik Anderson Tvedt, Fredrik Schjesvold
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Induction therapy followed by autologous stem cell transplantation (ASCT) is standard of care for young, fit patients with newly diagnosed multiple myeloma. Both bortezomib-lenalidomide-dexamethasone (VRd) and bortezomib-cyclophosphamide-dexamethasone (VCd) are widely in use, although none of them are EMA approved. Prospective studies comparing these regimens are lacking. In Norway, most regions used VCd as induction therapy for about a decade. However, the Oslo region shifted towards VRd in recent years, based on data showing that the combination of immunomodulatory drugs and proteasome inhibitors have the highest response rates (Moreau, Blood 2016). Aims: The aim of the study was to compare the regimens VCd and VRd as induction therapy before ASCT using population-based data from Norway. We hypothesized that VRd, compared to VCd, would lead to higher response rates and less need to change therapy, which again could improve progression-free survival (PFS) and overall survival (OS). Methods: We included all patients in Norway who received ASCT for newly diagnosed multiple myeloma in the period January 1st 2008 to December 31th 2020. Using electronic journals, we collected data from all transplant centers in Norway. The primary endpoint was the difference in response rates between VRd and VCd before ASCT and 3 months after ASCT. The co-primary endpoint was the difference between VRd and VCd in failure. We defined failure as either 1) change of induction therapy or 2) poor response (less than very good partial response (VGPR) at 3 months after ASCT). Secondary endpoints were differences in PFS and OS. Results: We identified 1354 patients who received ASCT as first-line treatment for multiple myeloma in Norway in the study period. Of these, 682 patients received VCd induction and 332 VRd induction. Response rates after induction therapy were higher with VRd vs VCd, with 73% of patients in the VRd group achieving ≥VGPR before ASCT, vs 47% in the VCd group (p<0.001). Three months after ASCT, response rates were also higher with VRd, with 89% in the VRd group achieving ≥VGPR, vs 75% in the VCd group (p<0.001). In the VCd group, 193 of 646 patients (30%) were classified as failure, significantly higher than in the VRd group, where 51 of 330 (15%) of patients were classified as failure (p<0.001). The difference in failure was mainly because VCd-patients more often achieved <VGPR 3 months after ASCT (22% of patients vs 10% of patients in the VRd group, p<0.001), and not because those who started VCd changed therapy more frequently (7% vs 5% for VCd vs VRd, p=0.250) Patients in the VRd group were more likely to receive further first-line treatment after ASCT (63% vs 14%) than in the VCd group; consolidation treatment (23% vs 1%), maintenance treatment (26% vs 10%) or both (14% vs 3%) were all more frequent in the VRd group. The 3-year PFS was significantly higher in the VRd group (67% vs 40%, p <0.001). As the VRd group more often received maintenance therapy, we did a separate analysis excluding patients who had received maintenance therapy. In this analysis, the 3-year PFS was still significantly higher with VRd (60% vs 36%, p <0.001). After a median follow-up of 89 months in the VCd group and 39 months in the VCd group, the median OS was not reached in either group. The 3-year OS was higher with VRd (92% vs 85%, p = 0.02) Summary/Conclusion: In this population-based, retrospective study including all patients who received first-line ASCT in Norway from 2008 to 2020, we found that patients treated with VRd induction therapy had higher response rates both before ASCT and after ASCT, as well as significantly better 3-year PFS and OS, compared to VCd.Keywords: Real world data, Induction, Multiple myeloma